Browse by author
Lookup NU author(s): Dr Sally Coulthard, Dr Christopher Howell, Jill Robson, Dr Andrew Hall
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The level of expression of the enzyme thiopurine methyltransferase (TPMT) is an important determinant of the metabolism of thiopurines used in the treatment of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), Studies in red blood cells (RBC) have shown that TPMT expression displays genetic polymorphism with 11% of individuals having intermediate and one in 300 undetectable levels. The genetic basis for this polymorphism has now been elucidated and polymerase chain reaction (PCR)-based assays described for the most common mutations accounting for reduced activity. In previous studies, genotype has been correlated with red blood cell activity. In this report, we describe the relationship between genotype and TPMT activity measured directly in the target of drug action, the leukemic cell. We have demonstrated that the TPMT activity in lymphoblasts from 38 children and adults found by PCR to be homozygotes (*1/*1) was significantly higher than that in the five heterozygotes (*1/*3) detected (median, 0.25 v 0.08, P < .002, Mann-Whitney U), Similar results were obtained when results from children were analyzed separately, However, comparison of activity in blasts from AML and ALL showed a higher level in the former (0.35 v 0.22 nU/mg, P < .002, n = 17, 35), suggesting that facto rs other than genotype may also influence expression. (C) 1998 by The American Society of Hematology.
Author(s): Coulthard SA, Howell CI, Robson J, Hall AG
Publication type: Article
Publication status: Published
Journal: Blood
Year: 1998
Volume: 92
Issue: 8
Pages: 2856-2862
Print publication date: 01/10/1998
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
URL: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/92/8/2856
PubMed id: 9763570
